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Abnormal intestinal permeability in pregnant patients with treated celiac disease
W1383
Moreower, the assessment of the intestinal mucosa is still required m confirm the presence of a gluten-sensitive enteropathy. (*) This study is a part of an European Project (CoeliacEU/cluster) financed by the EU (contract QLRTA999-00037).
The Rate of Relapse aher the Gluten Challenge in Patients Suspected to Have Celiac Disease: Are There Any Age Ditterences? Zrmjka Mi~k, Sanja Kolacek Miljana Percl, Oleg jadresin, josip Grgnrie, Aleksandra Klobucar
W1386
Celiac disease (CD) is a permanent intestinal intolerance to dietary wheat ghadin and related proteins that produce mucosal lesior~ in genetically susceptible indi~'iduals and is treated with fikdong gluteudree diet. It is suggested that CD in children bellow two years of age should be diagnosed tbfiowing fhe old ESPGAN criteria (diagnosis is based on findings of 3 small intestinal biopsies) while in those older than two years revised ESPGAN criteria (Just one small intestinal biopsy and a good clinical response on a gluten&ee die0 is sulBcietu, fhe aim of the study was to determine whether the incidence of patients whose diagnosis of CD was not contirrtmd by the third biopsy was influenced by patients age at the time of the hrst biopsy (when the diagnose was suspected). Patients and methods: In order to diagnose CD in 62 patients, irrespective of their age, the old ESPGAN criteria with at least three small intestinal biopsies were applied. According to the age at the time of the first biopsy patients were divided in two groups: Group A: those younger than 24 months (N = 49) and Group B: those older than 24 months (N = 13). Suction small intestinal biopsies were perlormed m the regiou of Treitz, and all biopsy samples were analysed by the same pathologist. Student T test was used to evaluate the difterences between the age groups. Resuhs: After 6 months of gluten challenge 13 patients in Group A (13/49 = 26,5~ had normal small intesnnal biopsy findings. Moreover, 7 of them (7/49 = i4%) are followed tot more than two years on uormal gluten containing diet and still do not have a histological relapse, in Group B (N = 13) 5 patients (38.5%) had a normal biopsy finding alter 6 months gluten challenge, and 3 of them (23%) are on a gluten containing diet for more than two ),ears, still without the histological relapse. Although the proportion of patients who did not have the histological relapse was higher in Group B, the difli:rence was not statistically significant after 6 months (p>0.05) nor after 24 months of gluten challenge (p>0.05). Conclusion: A high proportion of patients, irrespective of their age, did not have the histological relapse alter more than two years of gluten containing diet These results show that different diagusuc criteria tor patients younger and older than two years may be implausible.
Celiac Disease Antibodies in Patients with Sj6gren's Syndrome Adam F. Wolfe, Aaron E. Wolte, Melissa Reider-Demer, Elaine Monarch, Tania Gerarduzzi, Alessio Fasano, Micbelle M Pietzak Celiac disease (CD) is an immune-mediated enternpathy that occurs in genetically susceptible individuals who ingest gluten. CD is common in Europe and has been perceived as rare in the U.S. Patients with other autoimmune diseases are at higher risk for CD. Sjogren's syndrome is an autoimmune disease characterized by xerostomia (dry mouth), chronic arthritis and keratoconjunctivitis sicca (dry eyes). Aim: To screen subjects with SjOgren's Syndrome for CD with a questionnaire and serum antibodies, Methods: Subjects were enrolled at a Sj6grens syndrome support group meeting in Los Angeles. informed consent was obtained from subjects, and a questionnaire was used to collect data on the patient's symptoms, medical history and family histoD'. Sernm antigliadin lgG and IgA (AGA) and human anti-tissue transglutaminase IgG and lgA (htTG) were measured by ELISA. lgA antiendomysial (AEA) antibodies were detected by"indirect immnnofluorescence using human umbilical cord vein. Total lgA was measured on those who had very low AGA or htTG lgA levels. Small bowel biopsy was recommended to confirm the diagnosis in subjects who were AEA and htTG +, or AGA lgG + with total IgA deficiency. Results: Out of the 79 female subjects enrolled, 2 had serology consistent wifh CD (AEA+ and AEA/tTG IgA + ). One was Caucasian and one was Caucasian and Hispanic. Both patients complained of weakness, fatigue, diarrhea, gaseousness, joint pain and abdominal pain, and had thyroid disease and osteopornsis. One also had short stature and systemic lupus erythematosus. Their family histories were significant for arthritis, IDDM, thyroid disease, osteoporosis, and colon cancer One patient had the diagnosis of CD confirmed with a small bowel biopsy. 77 subjects had serology inconsistent with CD (57 with no positive antibodies, 16 with isolated AGA IgA+, 2 with AGA lgG/lgA+, 1 with AGA IgA/tTG lgA+, and 1 with isolated tTG IgA + ). However, symptoms and co-morbid conditions associated with CD were common: weakness (93%), joint pain (82%), diarrhea (65%), irritable bowel syndrome (32%), thyroid disease(30%), and recurrent abdominal pain (25%). Family histories were significant for arthritis (66%), IDDM (39%), thyroid disease (32%), and irritable bowel syndrmne (32%). Conclusions: Patients with Sjogrens syndrome possess many of the symptoms, family histories and co-morbid conditions associated with CD. In our small cohort, 2.5% of the subjects had serology consistent with CD. Prospective screening using serum antibodies may be the only way to identify CD in this patient population.
W1384 Detection of Autoantibodies against Enterocyte Actin Filaments as Serological Predictive Test tot Intestinal Villous Atrophy in Celiac Disease: Results of a Polycentric Stud)`" Maria G. Cleruente, Maria P Musu, Riccardo Troncone CarolH~ Ciacci, Tarcism Not, Elena Neri, Pierre Striscinglio, Gmseppe Maggiore, Lucia Cicotto, Gabriella Sole, Giovanm Gasbatriin, Girm R. Corazza, Umberto Volta, Alessio Fasano, Stetano De VirgdiLs Background Autoantfltodies against actin tilaments (,,K4A) have been described in celiacs with more severe degrees of intestinal mucosa lesions. We present the resuhs of a polycentric study desigoed to validate AAA detection as serological test for intestinal villous atrophy (lVA) in celiac disease. Methods We prospectively studied 299 and retrospectively' 84 selected serum samples {rmn biopsed proven cefiacs (anti-gliadin Ab (AGA), anti-endomystal kb (EMA) and anti-transgtmamn~a~ Ah (TGA) positives) and from biopsied not celiac patients il'om 10 ditlerent gastroenterulogy centers (6 pediatrics). All samples were blinded evaluated tn~ AAA using a new developed and more sensitive method of indirect immunofluoresx ence performed on enterocytes cuhured m presence of colchicine, a potent inducer of intraceilutat actin poiymerisation. Results The overall AAA posuivity observed in celiac patients was 82.5% AA,~ were positive in 982% of celiacs with fiat mucosa, in 89% of celiacs with moderate and m 30% ot celiacs with mild villous atrophy, but only in one AEA positive but biopsy negative patient AAA positivity significantly correlated with IVA (p<0 000 in the prospective study, p=0.005 in the retrospective study) with a positive predigtive value (PPV) of 99 4% and a negative predieuve value (NPV) of 87.5%. Conclusions. Our results coniirmed AKA as serological predictive test for IVA m celiac disease and indicate that AAA detection could Mve a high diagnostic value if considered as a second step test in the algorithm bar celiac disease diagnosis, to be used only" in patients positives for A(_iA, EMA and/or TGA, in order to predict the presence of IVA betore performing the intestinal biopsy.
w1387 Abnormal Intestinal Permeability in Pregnant Patients with Treated Celiac Disease Edgardo Smecuol, Horacio Vazquea, Emilia Sugai, Soina Niveloni, Nancy Tesei, Maria L. Moreno, Roberto Mazure, Eduardo Maurino, Jon Meddings, Julio C. Bai BACKGROUND: The onset or tlare-up of intestinal inflammatory disorders frequemly occurs during pregnancy or the puerperium in this context, we assessed that up to 20% of untreated celiac disease (CD) women are unmasked or exacerbated during these periods. We postulate that this effect could be related to an increased intestinal permeability.. However, the behavior of the gut permeability during pregnancy has trot been explored yet. AIM: To determine changes in intestinal permeability" during pregnancy and the puerperium both in patients with CD and healthy controls, MATERIALS: We evaluated clinical, biochemical, serological (antighadin --AGA- and endomysial --EmA- antibodies) parameters and intestinal permeability (Lactulose/mannitol test --Lac/mam) in a series of 28 pregnant patients with treated CD and 15 pregnant healthy" controls. At the time of inclusion, all patients reported to be on gluten restriction for more than two years. Detailed information on the status of maternal health and degree of compliance with the diet was obtained throughout the pregnancy. A clinical interview and Lac/man test and serology were obtained to either or both trimesters during pregnancy and 1-month after delivery. Adherence to the diet was monitored by a dietician and alsu based on the interview and the use of serology, RESULTS: Based on these criteria, 22 CD patients who were considered on strict gluten restriction underwent a total of 40 permeability tests. Eleven patients pertbrmed more than one test. Based on the normal Laffman ratio (<0.025), 1/6, 5/17, 7/10 and 5/7 samples had abnormal permeability tests at 1st, 2nd, 3rd trimester and the puerperium, respectively, Data from those patients with more than one determination confirm that abnormal permeability is more prevalent at the end of pregnancy and the puerpenum. Patients had no deterioration of the clinical status during pregnancy. In the heahhy cotttml group, 1/10 and 2/3 measurements showed abnormall)`, increased permeability at the 2nd and 3rd trimester, respectively CONCLUSIONS: Our original results show the presence of an abnornually increased intestinal permeability in pregnant women with treated and inactive CD. This efli:ct seems to be more pronounced with the advance of pregnancy and at the puerperium These finding and those of some health),- control pregnant women with abnormal permeability suggests that it could be a constitutional phenomenon associated with pregnancy predisposing to the onset or relapse of CD during these periods.
W1385 Anti-human lgA "lissne Transglutaminase Antibodies as Screening Test for Cneliae Disease Efisabetta Fabiani, Eglziano Pemzzi, Clementina Rondina, lvano Lorenzini, Renato Galeazzi, Gabnele Garbuglia, ltalo Bearzi, Giovanni Valemino Coppa, Carlo Catassi Background Recent studies have showo that the anti-human tissue transgltuaminase (tTG)antibodios detennination is a highly specific and sensitive tool for the diagnosis and followup of codiac disease (CD). However, so tar the use of this test for the CD screening in the general population has not been evaluated yet. Aim To evaluate the prevalence of CD in the general population using the IgA anti-hmnan tTG antibodies as first level screening test. Sut~ect. The study sample consisted of a heahhy population sample of all ages living in Camerano (Ancona, Italy)(*) Methods. IgA anti-human tTG test peflbrmed by an ELISA technique using a commercially available kit (Eu-tTG Eurospital, Trieste,Italy). All positive cases (Eu-tTG >7 UA.) were fimherly evaluated by the IgrAanti-endomysium antibodies (lgA-EMA) test and the intestinal biopsy. Results: 3712 subjects (57% F,43% M; 1-94 ),,ears) were screen{,d ior Cl) Fhe lgA anti-human tTG were negative in 2876/2897 (99%) tested sera, while 21 of them(l%) showed posmve values 16 out of 21 subiects underwent the intestinal biopsy so tat and C[) was lonnd in 8 ot them(all were IgA-EMA positive). As far as the intestinal lnstoiogy is concerned, in 3/8 a partial vollous atrophy was found, while the remaining 5 showed a fiat mueosa. Conclusions. The preliminary results of this study show that the i ~ ann-human r i g test seems to be a good first level screening tool for identifying sublects requiring a seconddee-el investigation (IgA-EMA and intestinal biopsy').
AGA
Abstracts
A-660
Moreower, the assessment of the intestinal mucosa is still required m confirm the presence of a gluten-sensitive enteropathy. (*) This study is a part of an European Project (CoeliacEU/cluster) financed by the EU (contract QLRTA999-00037).
The Rate of Relapse aher the Gluten Challenge in Patients Suspected to Have Celiac Disease: Are There Any Age Ditterences? Zrmjka Mi~k, Sanja Kolacek Miljana Percl, Oleg jadresin, josip Grgnrie, Aleksandra Klobucar
W1386
Celiac disease (CD) is a permanent intestinal intolerance to dietary wheat ghadin and related proteins that produce mucosal lesior~ in genetically susceptible indi~'iduals and is treated with fikdong gluteudree diet. It is suggested that CD in children bellow two years of age should be diagnosed tbfiowing fhe old ESPGAN criteria (diagnosis is based on findings of 3 small intestinal biopsies) while in those older than two years revised ESPGAN criteria (Just one small intestinal biopsy and a good clinical response on a gluten&ee die0 is sulBcietu, fhe aim of the study was to determine whether the incidence of patients whose diagnosis of CD was not contirrtmd by the third biopsy was influenced by patients age at the time of the hrst biopsy (when the diagnose was suspected). Patients and methods: In order to diagnose CD in 62 patients, irrespective of their age, the old ESPGAN criteria with at least three small intestinal biopsies were applied. According to the age at the time of the first biopsy patients were divided in two groups: Group A: those younger than 24 months (N = 49) and Group B: those older than 24 months (N = 13). Suction small intestinal biopsies were perlormed m the regiou of Treitz, and all biopsy samples were analysed by the same pathologist. Student T test was used to evaluate the difterences between the age groups. Resuhs: After 6 months of gluten challenge 13 patients in Group A (13/49 = 26,5~ had normal small intesnnal biopsy findings. Moreover, 7 of them (7/49 = i4%) are followed tot more than two years on uormal gluten containing diet and still do not have a histological relapse, in Group B (N = 13) 5 patients (38.5%) had a normal biopsy finding alter 6 months gluten challenge, and 3 of them (23%) are on a gluten containing diet for more than two ),ears, still without the histological relapse. Although the proportion of patients who did not have the histological relapse was higher in Group B, the difli:rence was not statistically significant after 6 months (p>0.05) nor after 24 months of gluten challenge (p>0.05). Conclusion: A high proportion of patients, irrespective of their age, did not have the histological relapse alter more than two years of gluten containing diet These results show that different diagusuc criteria tor patients younger and older than two years may be implausible.
Celiac Disease Antibodies in Patients with Sj6gren's Syndrome Adam F. Wolfe, Aaron E. Wolte, Melissa Reider-Demer, Elaine Monarch, Tania Gerarduzzi, Alessio Fasano, Micbelle M Pietzak Celiac disease (CD) is an immune-mediated enternpathy that occurs in genetically susceptible individuals who ingest gluten. CD is common in Europe and has been perceived as rare in the U.S. Patients with other autoimmune diseases are at higher risk for CD. Sjogren's syndrome is an autoimmune disease characterized by xerostomia (dry mouth), chronic arthritis and keratoconjunctivitis sicca (dry eyes). Aim: To screen subjects with SjOgren's Syndrome for CD with a questionnaire and serum antibodies, Methods: Subjects were enrolled at a Sj6grens syndrome support group meeting in Los Angeles. informed consent was obtained from subjects, and a questionnaire was used to collect data on the patient's symptoms, medical history and family histoD'. Sernm antigliadin lgG and IgA (AGA) and human anti-tissue transglutaminase IgG and lgA (htTG) were measured by ELISA. lgA antiendomysial (AEA) antibodies were detected by"indirect immnnofluorescence using human umbilical cord vein. Total lgA was measured on those who had very low AGA or htTG lgA levels. Small bowel biopsy was recommended to confirm the diagnosis in subjects who were AEA and htTG +, or AGA lgG + with total IgA deficiency. Results: Out of the 79 female subjects enrolled, 2 had serology consistent wifh CD (AEA+ and AEA/tTG IgA + ). One was Caucasian and one was Caucasian and Hispanic. Both patients complained of weakness, fatigue, diarrhea, gaseousness, joint pain and abdominal pain, and had thyroid disease and osteopornsis. One also had short stature and systemic lupus erythematosus. Their family histories were significant for arthritis, IDDM, thyroid disease, osteoporosis, and colon cancer One patient had the diagnosis of CD confirmed with a small bowel biopsy. 77 subjects had serology inconsistent with CD (57 with no positive antibodies, 16 with isolated AGA IgA+, 2 with AGA lgG/lgA+, 1 with AGA IgA/tTG lgA+, and 1 with isolated tTG IgA + ). However, symptoms and co-morbid conditions associated with CD were common: weakness (93%), joint pain (82%), diarrhea (65%), irritable bowel syndrome (32%), thyroid disease(30%), and recurrent abdominal pain (25%). Family histories were significant for arthritis (66%), IDDM (39%), thyroid disease (32%), and irritable bowel syndrmne (32%). Conclusions: Patients with Sjogrens syndrome possess many of the symptoms, family histories and co-morbid conditions associated with CD. In our small cohort, 2.5% of the subjects had serology consistent with CD. Prospective screening using serum antibodies may be the only way to identify CD in this patient population.
W1384 Detection of Autoantibodies against Enterocyte Actin Filaments as Serological Predictive Test tot Intestinal Villous Atrophy in Celiac Disease: Results of a Polycentric Stud)`" Maria G. Cleruente, Maria P Musu, Riccardo Troncone CarolH~ Ciacci, Tarcism Not, Elena Neri, Pierre Striscinglio, Gmseppe Maggiore, Lucia Cicotto, Gabriella Sole, Giovanm Gasbatriin, Girm R. Corazza, Umberto Volta, Alessio Fasano, Stetano De VirgdiLs Background Autoantfltodies against actin tilaments (,,K4A) have been described in celiacs with more severe degrees of intestinal mucosa lesions. We present the resuhs of a polycentric study desigoed to validate AAA detection as serological test for intestinal villous atrophy (lVA) in celiac disease. Methods We prospectively studied 299 and retrospectively' 84 selected serum samples {rmn biopsed proven cefiacs (anti-gliadin Ab (AGA), anti-endomystal kb (EMA) and anti-transgtmamn~a~ Ah (TGA) positives) and from biopsied not celiac patients il'om 10 ditlerent gastroenterulogy centers (6 pediatrics). All samples were blinded evaluated tn~ AAA using a new developed and more sensitive method of indirect immunofluoresx ence performed on enterocytes cuhured m presence of colchicine, a potent inducer of intraceilutat actin poiymerisation. Results The overall AAA posuivity observed in celiac patients was 82.5% AA,~ were positive in 982% of celiacs with fiat mucosa, in 89% of celiacs with moderate and m 30% ot celiacs with mild villous atrophy, but only in one AEA positive but biopsy negative patient AAA positivity significantly correlated with IVA (p<0 000 in the prospective study, p=0.005 in the retrospective study) with a positive predigtive value (PPV) of 99 4% and a negative predieuve value (NPV) of 87.5%. Conclusions. Our results coniirmed AKA as serological predictive test for IVA m celiac disease and indicate that AAA detection could Mve a high diagnostic value if considered as a second step test in the algorithm bar celiac disease diagnosis, to be used only" in patients positives for A(_iA, EMA and/or TGA, in order to predict the presence of IVA betore performing the intestinal biopsy.
w1387 Abnormal Intestinal Permeability in Pregnant Patients with Treated Celiac Disease Edgardo Smecuol, Horacio Vazquea, Emilia Sugai, Soina Niveloni, Nancy Tesei, Maria L. Moreno, Roberto Mazure, Eduardo Maurino, Jon Meddings, Julio C. Bai BACKGROUND: The onset or tlare-up of intestinal inflammatory disorders frequemly occurs during pregnancy or the puerperium in this context, we assessed that up to 20% of untreated celiac disease (CD) women are unmasked or exacerbated during these periods. We postulate that this effect could be related to an increased intestinal permeability.. However, the behavior of the gut permeability during pregnancy has trot been explored yet. AIM: To determine changes in intestinal permeability" during pregnancy and the puerperium both in patients with CD and healthy controls, MATERIALS: We evaluated clinical, biochemical, serological (antighadin --AGA- and endomysial --EmA- antibodies) parameters and intestinal permeability (Lactulose/mannitol test --Lac/mam) in a series of 28 pregnant patients with treated CD and 15 pregnant healthy" controls. At the time of inclusion, all patients reported to be on gluten restriction for more than two years. Detailed information on the status of maternal health and degree of compliance with the diet was obtained throughout the pregnancy. A clinical interview and Lac/man test and serology were obtained to either or both trimesters during pregnancy and 1-month after delivery. Adherence to the diet was monitored by a dietician and alsu based on the interview and the use of serology, RESULTS: Based on these criteria, 22 CD patients who were considered on strict gluten restriction underwent a total of 40 permeability tests. Eleven patients pertbrmed more than one test. Based on the normal Laffman ratio (<0.025), 1/6, 5/17, 7/10 and 5/7 samples had abnormal permeability tests at 1st, 2nd, 3rd trimester and the puerperium, respectively, Data from those patients with more than one determination confirm that abnormal permeability is more prevalent at the end of pregnancy and the puerpenum. Patients had no deterioration of the clinical status during pregnancy. In the heahhy cotttml group, 1/10 and 2/3 measurements showed abnormall)`, increased permeability at the 2nd and 3rd trimester, respectively CONCLUSIONS: Our original results show the presence of an abnornually increased intestinal permeability in pregnant women with treated and inactive CD. This efli:ct seems to be more pronounced with the advance of pregnancy and at the puerperium These finding and those of some health),- control pregnant women with abnormal permeability suggests that it could be a constitutional phenomenon associated with pregnancy predisposing to the onset or relapse of CD during these periods.
W1385 Anti-human lgA "lissne Transglutaminase Antibodies as Screening Test for Cneliae Disease Efisabetta Fabiani, Eglziano Pemzzi, Clementina Rondina, lvano Lorenzini, Renato Galeazzi, Gabnele Garbuglia, ltalo Bearzi, Giovanni Valemino Coppa, Carlo Catassi Background Recent studies have showo that the anti-human tissue transgltuaminase (tTG)antibodios detennination is a highly specific and sensitive tool for the diagnosis and followup of codiac disease (CD). However, so tar the use of this test for the CD screening in the general population has not been evaluated yet. Aim To evaluate the prevalence of CD in the general population using the IgA anti-hmnan tTG antibodies as first level screening test. Sut~ect. The study sample consisted of a heahhy population sample of all ages living in Camerano (Ancona, Italy)(*) Methods. IgA anti-human tTG test peflbrmed by an ELISA technique using a commercially available kit (Eu-tTG Eurospital, Trieste,Italy). All positive cases (Eu-tTG >7 UA.) were fimherly evaluated by the IgrAanti-endomysium antibodies (lgA-EMA) test and the intestinal biopsy. Results: 3712 subjects (57% F,43% M; 1-94 ),,ears) were screen{,d ior Cl) Fhe lgA anti-human tTG were negative in 2876/2897 (99%) tested sera, while 21 of them(l%) showed posmve values 16 out of 21 subiects underwent the intestinal biopsy so tat and C[) was lonnd in 8 ot them(all were IgA-EMA positive). As far as the intestinal lnstoiogy is concerned, in 3/8 a partial vollous atrophy was found, while the remaining 5 showed a fiat mueosa. Conclusions. The preliminary results of this study show that the i ~ ann-human r i g test seems to be a good first level screening tool for identifying sublects requiring a seconddee-el investigation (IgA-EMA and intestinal biopsy').
AGA
Abstracts
A-660